EVENTS

An East Texas school maintenance worker was in fair condition Thursday after being accidentally shot during a district-sponsored handgun safety class, according to local media.

The concealed handgun license class is part of an effort to permit teachers to carry firearms in schools in Van, Texas, the Tyler Morning Telegraph reported.

KLTV identified the maintenance department employee as Glenn Geddie, and reported him hospitalized in fair condition.

These dumshitte loonie redneck morons can’t even keep from shooting their motherfucken selves, but they are gonna “protect the children” when another dumshitte loonie redneck moron comes blasting into the school with a motherfucken assault rifle?

We have been living in the “no-A2″ regime for a number of years now, where NIH grant applicants are only allowed a single opportunity to respond to the reviews of their initial grant submissions with a revised version. If that single revised version does not get funded, it is impermissible to revise it by responding to the reviews and resubmitting a second revised version. At that point you can only write a “new” grant, which has to be substantially different from the unfunded one.

I have had a lot of experience in this regime dealing with my own grants as well consulting on those of colleagues and reviewing them in study section. Based on this experience I have arrived at the following two rules that should only in exceedingly rare circumstances be violated:

(1) If the signifiance criterion scores from the assigned reviewers on the initial grant submission were the *best* scores, and you were hammered on approach, then you have a chance, and it is worth revising and resubmitting. If, however, the significance scores were the *worst* scores, and this was driven by fundamental concerns about the impact of the planned research, then revision and resubmission is unwise. The better course is to rethink the presentation of the overall thrust of the planned research and submit as a new application. This is because it is generally impossible to convince reviewers that they were flat-out wrong about their conclusions that your proposed research is fundamentally uninteresting.

(2) Regardless of what is driving the scoring, if in order to successfully respond to reviewer concerns, you find yourself completely reorienting the thrust of two or more of the specific aims–for example, by discarding experimental approaches wholesale and employing different ones, or by replacing entire hypotheses with other ones–you should submit as a new grant. This is because you don’t want to waste an opportunity to revise and resubmit multiple brand new aims at least once with an explicit response to reviewer concerns regarding those particular specific aims. If you submit these brand new aims in a resubmission, then you lose that opportunity.

(3) You need to get detailed case-specific advice about this shitte from people who have a lot of experience with the new no-A2 regime, not from olde geezers who have been renewing the same single R01 for decades.

Over on the twitterz, DrugMonkey is sparring with some loonie pit bull enthusiasts. Sadly, their best argument seems to be “well, even yorkies maim people”. Hmm, now where have I heard this before? Oh, right.

I dreamt last night that I was Ringo Starr, and I was jumping up and down yelling and screaming at George Martin, “You will pay for the goddamn shitte thatte we need and you will buy it WHEN WE NEED ITTE, GODDAMMITTE!” And then I snapped a drumstick in two over my knee–it took three slams to finish itte offe–and then flung the pieces at him and stormed out of the room.

I must be repressing rage about the sequester about to hit NIH and thereby dickepunche my non-competing renewals and totally kill the competing award I have pending after council review. (And yes, I am aware that George Martin was the Beatles’ producer, not their manager; it was a motherfucken dream.)

Next morning, Monday, after disposing of the embalmed head to a barber, for a block, I settled my own and comrade’s bill; using, however, my comrade’s money. The grinning landlord, as well as the boarders, seemed amazingly tickled at the sudden friendship which had sprung up between me and Queequeg—especially as Peter Coffin’s cock and bull stories about him had previously so much alarmed me concerning the very person whom I now companied with.

We borrowed a wheelbarrow, and embarking our things, including my own poor carpet-bag, and Queequeg’s canvas sack and hammock, away we went down to “the Moss,” the little Nantucket packet schooner moored at the wharf. As we were going along the people stared; not at Queequeg so much—for they were used to seeing cannibals like him in their streets,—but at seeing him and me upon such confidential terms. But we heeded them not, going along wheeling the barrow by turns, and Queequeg now and then stopping to adjust the sheath on his harpoon barbs. I asked him why he carried such a troublesome thing with him ashore, and whether all whaling ships did not find their own harpoons. To this, in substance, he replied, that though what I hinted was true enough, yet he had a particular affection for his own harpoon, because it was of assured stuff, well tried in many a mortal combat, and deeply intimate with the hearts of whales. In short, like many inland reapers and mowers, who go into the farmers’ meadows armed with their own scythes—though in no wise obliged to furnish them—even so, Queequeg, for his own private reasons, preferred his own harpoon.

Shifting the barrow from my hand to his, he told me a funny story about the first wheelbarrow he had ever seen. It was in Sag Harbor. The owners of his ship, it seems, had lent him one, in which to carry his heavy chest to his boarding house. Not to seem ignorant about the thing—though in truth he was entirely so, concerning the precise way in which to manage the barrow—Queequeg puts his chest upon it; lashes it fast; and then shoulders the barrow and marches up the wharf. “Why,” said I, “Queequeg, you might have known better than that, one would think. Didn’t the people laugh?”

Upon this, he told me another story. The people of his island of Rokovoko, it seems, at their wedding feasts express the fragrant water of young cocoanuts into a large stained calabash like a punchbowl; and this punchbowl always forms the great central ornament on the braided mat where the feast is held. Now a certain grand merchant ship once touched at Rokovoko, and its commander—from all accounts, a very stately punctilious gentleman, at least for a sea captain—this commander was invited to the wedding feast of Queequeg’s sister, a pretty young princess just turned of ten. Well; when all the wedding guests were assembled at the bride’s bamboo cottage, this Captain marches in, and being assigned the post of honour, placed himself over against the punchbowl, and between the High Priest and his majesty the King, Queequeg’s father. Grace being said,—for those people have their grace as well as we—though Queequeg told me that unlike us, who at such times look downwards to our platters, they, on the contrary, copying the ducks, glance upwards to the great Giver of all feasts—Grace, I say, being said, the High Priest opens the banquet by the immemorial ceremony of the island; that is, dipping his consecrated and consecrating fingers into the bowl before the blessed beverage circulates. Seeing himself placed next the Priest, and noting the ceremony, and thinking himself—being Captain of a ship—as having plain precedence over a mere island King, especially in the King’s own house—the Captain coolly proceeds to wash his hands in the punchbowl;—taking it I suppose for a huge finger-glass. “Now,” said Queequeg, “what you tink now?—Didn’t our people laugh?”

At last, passage paid, and luggage safe, we stood on board the schooner. Hoisting sail, it glided down the Acushnet river. On one side, New Bedford rose in terraces of streets, their ice-covered trees all glittering in the clear, cold air. Huge hills and mountains of casks on casks were piled upon her wharves, and side by side the world-wandering whale ships lay silent and safely moored at last; while from others came a sound of carpenters and coopers, with blended noises of fires and forges to melt the pitch, all betokening that new cruises were on the start; that one most perilous and long voyage ended, only begins a second; and a second ended, only begins a third, and so on, for ever and for aye. Such is the endlessness, yea, the intolerableness of all earthly effort.

Gaining the more open water, the bracing breeze waxed fresh; the little Moss tossed the quick foam from her bows, as a young colt his snortings. How I snuffed that Tartar air!—how I spurned that turnpike earth!—that common highway all over dented with the marks of slavish heels and hoofs; and turned me to admire the magnanimity of the sea which will permit no records.

At the same foam-fountain, Queequeg seemed to drink and reel with me. His dusky nostrils swelled apart; he showed his filed and pointed teeth. On, on we flew; and our offing gained, the Moss did homage to the blast; ducked and dived her bows as a slave before the Sultan. Sideways leaning, we sideways darted; every ropeyarn tingling like a wire; the two tall masts buckling like Indian canes in land tornadoes. So full of this reeling scene were we, as we stood by the plunging bowsprit, that for some time we did not notice the jeering glances of the passengers, a lubber-like assembly, who marvelled that two fellow beings should be so companionable; as though a white man were anything more dignified than a whitewashed negro. But there were some boobies and bumpkins there, who, by their intense greenness, must have come from the heart and centre of all verdure. Queequeg caught one of these young saplings mimicking him behind his back. I thought the bumpkin’s hour of doom was come. Dropping his harpoon, the brawny savage caught him in his arms, and by an almost miraculous dexterity and strength, sent him high up bodily into the air; then slightly tapping his stern in mid-somerset, the fellow landed with bursting lungs upon his feet, while Queequeg, turning his back upon him, lighted his tomahawk pipe and passed it to me for a puff.

“Look you,” roared the Captain, “I’ll kill-e YOU, you cannibal, if you try any more of your tricks aboard here; so mind your eye.”

But it so happened just then, that it was high time for the Captain to mind his own eye. The prodigious strain upon the main-sail had parted the weather-sheet, and the tremendous boom was now flying from side to side, completely sweeping the entire after part of the deck. The poor fellow whom Queequeg had handled so roughly, was swept overboard; all hands were in a panic; and to attempt snatching at the boom to stay it, seemed madness. It flew from right to left, and back again, almost in one ticking of a watch, and every instant seemed on the point of snapping into splinters. Nothing was done, and nothing seemed capable of being done; those on deck rushed towards the bows, and stood eyeing the boom as if it were the lower jaw of an exasperated whale. In the midst of this consternation, Queequeg dropped deftly to his knees, and crawling under the path of the boom, whipped hold of a rope, secured one end to the bulwarks, and then flinging the other like a lasso, caught it round the boom as it swept over his head, and at the next jerk, the spar was that way trapped, and all was safe. The schooner was run into the wind, and while the hands were clearing away the stern boat, Queequeg, stripped to the waist, darted from the side with a long living arc of a leap. For three minutes or more he was seen swimming like a dog, throwing his long arms straight out before him, and by turns revealing his brawny shoulders through the freezing foam. I looked at the grand and glorious fellow, but saw no one to be saved. The greenhorn had gone down. Shooting himself perpendicularly from the water, Queequeg, now took an instant’s glance around him, and seeming to see just how matters were, dived down and disappeared. A few minutes more, and he rose again, one arm still striking out, and with the other dragging a lifeless form. The boat soon picked them up. The poor bumpkin was restored. All hands voted Queequeg a noble trump; the captain begged his pardon. From that hour I clove to Queequeg like a barnacle; yea, till poor Queequeg took his last long dive.

Was there ever such unconsciousness? He did not seem to think that he at all deserved a medal from the Humane and Magnanimous Societies. He only asked for water—fresh water—something to wipe the brine off; that done, he put on dry clothes, lighted his pipe, and leaning against the bulwarks, and mildly eyeing those around him, seemed to be saying to himself—”It’s a mutual, joint-stock world, in all meridians. We cannibals must help these Christians.”

This is the basket ricotta we use from Bellwether Farms. The fucken shitte is good!

Sautee the onions and garlic in olive oil with red and black pepper, thyme, and rosemary, and a little salt, until they are nice and soft and starting to turn golden.

Deglaze with the wine.

When most of the liquid is reduced off, add the tomatoes.

Stir well, and simmer on low with the lidde offe.

After a little while, add some of the basil.

Salad: radicchio, endive, salt, pepper, olive oil, and balsamic vinegar. I only dress this lightly, as the radicchio and endive have such lovely flavors, you don’t want to fucke with itte too much.

Sauce looks done!

Throw in a half to three-fourths of a cup of pasta water and the drained rigatoni (stopping boiling them when they are very molto al dente), turn up the heat to medium high, and finish them with gentle stirring for about two minutes.

Turn off the heat and add some nice dollops of the ricotta. We used about half the container (which was twelve ounces by weight, so we used about six ounces). Stir gently until it is fully incorporated.

Plate, sprinkle, and grate (this is pecorino moliterno). You can see there is some nice broth in the dish, based on the amount of pasta water I added. I love this sauce brothy like that, as I think it opens up the flavor of the ricotta, but if you want it thicker, just add less water at that stage.

uBiome claims that they are exempt from IRB review because their “primary purpose” is to provide a service to private parties for a fee, and that their subsequent analysis of the data collected is an incidental “meta-analysis”:

However, IRB approval is not required for us to provide our primary service of microbiome compositional analysis and interpretation for private parties. Thus, our sample collection is part of a service and our research study is a meta-analysis of de-identified data, which is technically exempt from IRB.

H+: You are looking for funding via Indiegogo. Can you tell me a bit about the project you are looking to fund specifically and describe what funders will receive? Why did you choose Indiegogo over other services, i.e. Kickstarter?

Jessica: We are looking to crowdfund our citizen science project at www.indiegogo.com/ubiome. For $79, you can sequence your GI tract; for $235, you can sequence the GI tract three times; for $272 you can sequence all five sites: mouth, ears, nose, GI tract, and genitals. Here’s how it works: You pledge and we send you a sample kit. You swipe the sample brush across the corresponding sample site. The cells are lysed in solution and sent to our laboratory for processing. Once we’ve sequenced your sample, we’ll send a login to our website where you can visualize and understand your data. As a uBiome community member you find out about our latest discoveries first, participate in ongoing citizen science projects, and suggest new questions that we can address together. We chose Indiegogo because they are international, flexible and have great customer service. However, we hope that a lot more citizen science projects will come online, on any platform.

[Emphasis added.] In case it wasn’t obvious enough already, these public statements by Jessica Richman, a uBiome principal, make it absolutely clear that a primary purpose of the uBiome project is scientific research inquiry, and is far from incidental. And also, the claim that study participants are not recruited or enlisted until the kits are used to collect tissue/fluid samples and returned is also a load of horseshit: note all the uses in this public statement of “you” to refer to the same person paying the fee, receiving the kit, sending in the tissue/fluid samples, and thereby contributing thir microbiome sequences to uBiome’s “discoveries”.

uBiome has posted a public statement concerning IRB review and approval of their human studies research on their third-party Web site from which they have–as viewed by some who have considered the situation–already been recruiting and enlisting study participants from whom they have already received > $300,000 in participation fees:

Does uBiome have an Institutional Review Board?

Balancing the needs of open access while maintaining your safety and privacy is very important. To achieve this end, we are working with an independent Institutional Review Board (IRB) to provide ethical oversight. We will provide complete details when this process is complete.

Isn’t IRB oversight required before a study can begin?

IRB oversight is used to make sure a study is ethically sound before it begins. Our IRB will be completed before any kits are sent out and before any consent forms are signed. We will release our consent forms when we have final IRB approval.

However, IRB approval is not required for us to provide our primary service of microbiome compositional analysis and interpretation for private parties. Thus, our sample collection is part of a service and our research study is a meta-analysis of de-identified data, which is technically exempt from IRB. That said, we are doing full Board review to insure that every aspect of the project is ethically safe and sound.

If uBiome accepted any federal funding or was a university research laboratory instead of a citizen science startup, the IRB review would indeed be mandatory. As it is, this review should only strengthen uBiome as a research study and as a community.

I will leave it to the reader, and particularly any experts on IRB compliance, whether their argument that they are exempt from IRB oversight and, in particular, the following syllogism hold any water:

However, IRB approval is not required for us to provide our primary service of microbiome compositional analysis and interpretation for private parties. Thus, our sample collection is part of a service and our research study is a meta-analysis of de-identified data, which is technically exempt from IRB.

Here are some of my own thoughts on this argument (some of which have already been fleshed out and documented in my earlier blogge post):

(1) Their own Web site and their third-party “crowd-funding” site make it very clear that one of the main purposes–perhaps the primary purpose, on a reasonable reading–of their project and one of the major benefits to the participants they have already been recruiting is the aggregation and statistical analysis of the individual results so as to contribute novel information to the scientific understanding of the relationship between the human microbiome and human health/disease.

(2) My understanding is that the meta-analysis exemption applies solely to de-identified data obtained from other already-performed human subjects studies that themselves have been performed subject to appropriate IRB oversight, and that this exemption cannot possibly be applicable to a situation where the directors of a study collect human tissue/fluid samples, perform a biological analysis, and claim its “primary purpose” is a service to the participants, and that their subsequent aggregation and statistical analysis of the data that they collected is nothing but a meta-analysis.

I will also note that the following statement from one of the uBiome principals, Jessica, in her comment on my previous blogge post on this subject in which she points to their newly published IRB verbiage is pretty fucken hilarious, considering the bizarrely belligerent and legally threatening tone that was taken by the signatories Jessica, Zac, and Will in the e-mail to me I referred to earlier in which they “requested” that I not quote from any of their e-mails to me:

I appreciate the dialog here on this blog. Although I think the tone of the original blog post is unnecessarily combative, we are glad for the focus on ethical oversight, and share the goal that citizen science be conducted in a thoughtful, privacy-aware, and ethical manner.

A Brief History of Medical Research Ethics in the United StatesGregory Gadow

Comradde PhysioProffe has asked me to expand on this comment a bit and provide links.

First off, I’m on the Community Advisory Board (CAB) for the Seattle HIV Vaccine Trials Unit. CABs are found mostly in the context of HIV research but they are spreading to other areas; while an institutional review board (IRB) works to cover the collective ass of the researchers and make sure they are following federal law and world ethical standards, CABs work to protect the rights of study participants and to represent the voice of communities affected by human medical research. I’ve also been a participant in three different studies involving HIV vaccines; I mention this so folks will understand where my passion for the topic comes from.

During the war crimes trials in Nuremberg, the extent and depravity of Nazi human experientation came to light. As they were prosecuting these experiments as war crimes, the Council for War Crimes in 1947 set forth the Nuremberg Code. These ten points defined legitimate medical research and required, among other things, that it be done for the good of society, avoid unnecessary physical and mental suffering, be conducted only by scientifically qualified persons and always — ALWAYS — have the informed, voluntary consent of the test subjects without any element of force, fraud, deceit, duress or coersion.

While it was originally intended as a guideline for the trials, it became the basis for the Declaration of Helsinki, written by the World Medical Association and adopted in June, 1964. The Declaration has been revised several six times, most recently in October, 2008, and typically in response to major crises: the first, in 1975, was in response to the US’ own horrific research abuses (more on that below) while the fourth (1996) and fifth (2000) were in response to studies involving HIV/AIDS. The Declaration serves as the model for laws governing human medical experimentation in many countries.

The US dragged its heels on adopting the Declaration. Then in 1972, a scandal erupted over the Tuskegee syphilis experiment. This study, started in 1932 by the US Public Health Service, recruited 600 poor African-American tenant farmers in Macon County, Alabama: 201 of them were healthy and 399 had syphilis, which at the time was incurable. The purpose of the study was to try out treatments on what even the US government admitted to be a powerless, desperate demographic. Neither the men nor their partners were told that they had a terminal STD; instead, the sick men were told they had “bad blood” — a folk term with no basis in science — and that they would get free medical care for themselves and their families, plus burial insurance (i.e., a grave plot, casket and funeral), for helping to find a cure.

When penicillin was discovered, and found in 1947 to be a total cure for syphilis, the focus of the study changed from trying to find a cure to documenting the progress of the disease from its early stages through termination. The men and their partners were not given penicillin, as that would interfere with the new purpose: instead, the government watched them die a slow, horrific death as they developed tumors and the spirochete destroyed their brains and central nervous system. Those who wanted out of the study, or who had heard of this new miracle drug and wanted it, were told that dropping out meant paying back the cost of decades of medical care, a sum that was far beyond anything a sharecropper could come up with.

With the publicity surrounding the Declaration of Helsinki in 1964, people involved in the study began to question the ethical standards they were using. The passage of the Freedom of Information Act in 1966 allowed them and others to demand — and get — answers from the US government. The story made national headlines when the Washington Star published an expose on July 25, 1972, and the study was officially ended on November 6 of that year. In response to the scandal, the National Research Act of 1974 was passed, which made the institutional review board (IRB) a mandatory part of medical research in the US. The Act also created the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research to study the ethical and legal issues and make recommendations. The Commission’s final report was the Belmont Report of 1978 (text here), which was adopted by the Department of Health and Human Services as the Federal Policy for the Protection of Human Subjects, informally known as the Common Rule (because it is the set of rules common to all human experimentation in the United States.) The US government did not officially apologize until May 16, 1997, when President Clinton addressed five of the eight surviving study participants at a White House ceremony,

What was done cannot be undone. But we can end the silence. We can stop turning our heads away. We can look at you in the eye and finally say on behalf of the American people, what the United States government did was shameful, and I am sorry … To our African American citizens, I am sorry that your federal government orchestrated a study so clearly racist.

In summary, there are damned good reasons why IRBs are required in this country. Any and all efforts to avoid independent oversight should be viewed with very deep suspicion. At best, it is unethical; at worst…. Surely, I don’t need to elaborate on that. The Food and Drug Administration has a list of information sheets regarding IRBs.

I’m no lawyer, but it seems that uBiome’s own comments about keeping data and using it for research purposes puts it firmly in the arena of human medical research. This would be true even if they are just collecting data for the use of other researchers. Because federal law requires that information about a research group’s IRB be public, and because uBiome has been so cagey about releasing this information, is highly suspect.

Maybe it is time for the FDA and other appropriate federal agencies to get involved.

Regarding CABs, they appeared in the early 1990s in response to activism by groups such as ACT-UP!. The idea was to make sure that, despite the law, the gay community would not become the next group of Tuskegee sharecroppers. Today, most HIV research organizations around the world require that every unit involved in the research have a board of local laypeople to represent the community in the research process.